# US 12,758,561 B2 · Administration of benzodiazepine compositions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,758,561 B2 - Document ID: US12758561B2 - Status: Granted - Kind: B2 - Application number: 18/062,062 - Filed: 2022-12-06 - Published: 2023-04-06 - Granted: 2026-10-13 - Earliest claimed: 2008-03-28 - Assignees: Neurelis, Inc. - Applicants: Neurelis, Inc. - Inventors: Steve Cartt; David Medeiros; Garry Thomas Gwozdz; Andrew Loxley; Mark Mitchnick; David F. Hale; Edward T. Maggio - Web page: https://patentgrep.com/patent/US12758561B2 ## CPC - A61K 31/5513: 1,4-Benzodiazepines, e.g. diazepam {or clozapine} - A61K 8/678: {Tocopherol, i.e. vitamin E} - A61K 9/0043: {Nose} - A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]} - A61K 31/355: Tocopherols, e.g. vitamin E - A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The invention relates to pharmaceutical compositions comprising one or more benzodiazepine drugs for nasal administration, methods for producing and for using such compositions. ## Claims ### Claim 1 A pharmaceutical composition for intranasal administration comprising: a therapeutically effective amount of a benzodiazepine drug dissolved in about 30% to about 95% (w/w) of one or more natural or synthetic tocopherols or tocotrienols selected from the group consisting of α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, tocophersolan, any isomers thereof, any esters thereof and any combinations thereof, and about 10% to about 70% (w/w) of one or more alcohols or glycols, or any combinations thereof, and about 0.01% to about 1% (w/v) of an alkyl glycoside, wherein the pharmaceutical composition is a solution and contains less than 1% water, wherein the pharmaceutical composition is in a pharmaceutically-acceptable spray formulation. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the benzodiazepine is diazepam. ### Claim 3 (depends on 2) The pharmaceutical composition of claim 2, wherein the therapeutically effective amount of the diazepam is about 1 mg to about 20 mg. ### Claim 4 (depends on 2) The pharmaceutical composition of claim 2, wherein the therapeutically effective amount of the diazepam is about 2 mg to about 10 mg. ### Claim 5 (depends on 1) The pharmaceutical composition of claim 1, wherein the natural or synthetic tocopherols or tocotrienols are selected from the group consisting of: α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, tocophersolan, any isomers thereof, any esters thereof and any combinations thereof. ### Claim 6 (depends on 1) The pharmaceutical composition of claim 1, wherein the natural or synthetic tocopherols or tocotrienols is α-tocopherol. ### Claim 7 (depends on 1) The pharmaceutical composition of claim 1, wherein the one or more alcohols or glycols or any combinations thereof is selected from the group consisting of ethanol, propyl alcohol, butyl alcohol, pentanol, benzyl alcohol, isomers thereof and any combinations thereof. ### Claim 8 (depends on 1) The pharmaceutical composition of claim 1, wherein the therapeutically effective amount of the benzodiazepine drug is present in the pharmaceutical solution at a concentration of about 10 mg/mL to about 250 mg/mL. ### Claim 9 (depends on 1) The pharmaceutical composition of claim 1, wherein the benzodiazepine drug is present in the pharmaceutical solution at a concentration of about 20 mg/mL to about 50 mg/mL. ### Claim 10 (depends on 1) The pharmaceutical composition of claim 1, wherein the therapeutically effective amount of the benzodiazepine is about 1 mg to about 20 mg. ### Claim 11 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical solution comprises one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof in an amount from about 45% to about 85% (w/w). ### Claim 12 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical solution comprises one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof in an amount from about 60% to about 75% (w/w). ### Claim 13 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical solution comprises one or more alcohols or glycols, or any combinations thereof in an amount from about 15% to about 55% (w/w). ### Claim 14 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical solution comprises one or more alcohols or glycols, or any combinations thereof in an amount from about 25% to about 40% (w/w). ### Claim 15 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises at least one additional ingredient selected from the group consisting of stabilizers, coloring agents, pH adjusters, buffering agents, preservatives, wetting agents, flavoring agents and combinations thereof. ### Claim 16 (depends on 1) The pharmaceutical composition of claim 1, wherein the alkyl glycoside is selected from the group consisting of octyl α-D-maltoside, nonyl α-D-maltoside, decyl α-D-maltoside, undecyl α-D-maltoside, dodecyl α-D-maltoside, tridecyl α-D-maltoside, tetradecyl α-D-maltoside, pentadecyl α-D-maltoside, octadecyl α-D-maltoside, octyl α-D-glucoside, nonyl α-D-glucoside, decyl α-D-glucoside, undecyl α-D-glucoside, dodecyl α-D-glucoside, tridecyl α-D-glucoside, tetradecyl α-D-glucoside, pentadecyl α-D-glucoside, octadecyl α-D-glucoside, octyl α-D-sucroside, nonyl α-D-sucroside, decyl α-D-sucroside, undecyl α-D-sucroside, dodecyl α-D-sucroside, tridecyl α-D-sucroside, tetradecyl α-D-sucroside, pentadecyl α-D-sucroside, octadecyl α-D-sucroside, octyl β-D-maltoside, nonyl β-D-maltoside, decyl β-D-maltoside, undecyl β-D-maltoside, dodecyl β-D-maltoside, tridecyl β-D-maltoside, tetradecyl β-D-maltoside, pentadecyl β-D-maltoside, octadecyl β-D-maltoside, octyl β-D-glucoside, nonyl β-D-glucoside, decyl β-D-glucoside, undecyl β-D-glucoside, dodecyl β-D-glucoside, tridecyl β-D-glucoside, tetradecyl β-D-glucoside, pentadecyl β-D-glucoside, octadecyl β-D-glucoside, octyl β-D-sucroside, nonyl β-D-sucroside, decyl β-D-sucroside, undecyl β-D-sucroside, dodecyl β-D-sucroside, tridecyl β-D-sucroside, tetradecyl β-D-sucroside, pentadecyl β-D-sucroside, and octadecyl β-D-sucroside. ### Claim 17 (depends on 1) The pharmaceutical composition of claim 1, wherein the alkyl glycoside is selected from the group consisting of dodecyl maltoside, tetradecyl maltoside, sucrose dodecanoate, sucrose monostearate, sucrose distearate and any combinations thereof. ### Claim 18 (depends on 1) The pharmaceutical composition of claim 1, wherein the alkyl glycoside is dodecyl β-D-maltoside. ### Claim 19 (depends on 1) The pharmaceutical composition of claim 1, wherein the alkyl glycoside is present in the pharmaceutical composition at a concentration of about 0.05% to about 0.5% (w/v). ### Claim 20 (depends on 1) The pharmaceutical composition of claim 1, wherein the alkyl glycoside is present in the pharmaceutical composition at a concentration of about 0.125% to about 0.5% (w/v). ### Claim 21 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition dosage volume is about 25 μL to about 250 μL. ### Claim 22 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition dosage volume is about 50 μL to about 150 μL. ### Claim 23 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition dosage volume is about 100 μL. ### Claim 24 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition contains less than 0.5% water. ### Claim 25 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition contains less than 0.25% water. ### Claim 26 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition contains less than 0.1% water. ### Claim 27 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition contains no water.